Linked Life Data

20818336

Source:http://linkedlifedata.com/resource/pubmed/id/20818336

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2010-10-20
pubmed:abstractText
Myocardin-related transcription factors (MRTFs) are actin-regulated transcriptional coactivators, which bind G-actin through their N-terminal RPEL domains. In response to signal-induced actin polymerisation and concomitant G-actin depletion, MRTFs accumulate in the nucleus and activate target gene transcription through their partner protein SRF. Nuclear accumulation of MRTFs in response to signal is inhibited by increased G-actin level. Here, we study the mechanism by which MRTF-A enters the nucleus. We show that MRTF-A contains an unusually long bipartite nuclear localisation signal (NLS), comprising two basic elements separated by 30 residues, embedded within the RPEL domain. Using siRNA-mediated protein depletion in vivo, and nuclear import assays in vitro, we show that the MRTF-A extended bipartite NLS uses the importin (Imp)?/?-dependent import pathway, and that import is inhibited by G-actin. Interaction of the NLS with the Imp?-Imp? heterodimer requires both NLS basic elements, and is dependent on the Imp? major and minor binding pockets. Binding of the Imp?-Imp? heterodimer to the intact MRTF-A RPEL domain occurs competitively with G-actin. Thus, MRTF-A contains an actin-sensitive nuclear import signal.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-2075
pubmed:author
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3448-58
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
An actin-regulated importin ?/?-dependent extended bipartite NLS directs nuclear import of MRTF-A.
pubmed:affiliation
Transcription Laboratory, Cancer Research UK, London Research Institute, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't